The androgen axis in recurrent prostate cancer

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• Prostate cancer recurrence during androgen deprivation therapy (ADT) is termed androgen-independent.
• High expression of androgen receptor (AR) and AR-regulated genes in recurrent prostate cancer suggests AR signaling persists.
• Understanding AR and androgen roles in recurrence is crucial for developing effective treatments.

Purpose of the Study:

• To investigate androgen receptor expression and tissue androgen levels in recurrent prostate cancer during ADT.
• To determine if sufficient androgens are present to activate AR in recurrent prostate cancer.
• To explore the implications for novel therapeutic strategies.

Main Methods:

• Comparative analysis of prostate cancer specimens from 22 men with recurrent disease during ADT and 48 benign prostate specimens.
• Measurement of AR expression using monoclonal antibody and automated digital video image analysis.
• Quantification of tissue androgens (testosterone, dihydrotestosterone, dehydroepiandrosterone, androstenedione) via radioimmunoassay.

Main Results:

• AR expression (immunostaining) was similar in both recurrent prostate cancer and benign prostate tissues.
• Tissue testosterone levels were comparable between recurrent and benign prostate tissues.
• While dihydrotestosterone, dehydroepiandrosterone, and androstenedione were lower in recurrent prostate cancer, dihydrotestosterone levels remained sufficient (1.45 nM) to potentially activate AR, evidenced by prostate-specific antigen expression.

Conclusions:

• Sufficient levels of testosterone and dihydrotestosterone exist in recurrent prostate cancer tissue to activate the androgen receptor.
• Novel therapeutic strategies for recurrent prostate cancer should directly target the androgen receptor.
• Interventions aimed at preventing androgen formation within prostate cancer tissue are warranted.